• I love studying immune responses, especially to viral infections! As a graduate student, under the mentorship of Dr. Jeffery Frelinger at the University of North Carolina, I investigated the direct anti-viral roles of CD4 T cells and how they adopt cytotoxic effector activities. These were significant as they illustrated the plasticity of effector anti-viral CD4 T cells and highlighted that they could develop pathogenic cytolytic capabilities, which was arguably under-appreciated at the time. As a Postdoctoral Fellow in the laboratory of Dr. Rafi Ahmed at Emory University, I performed pioneering studies using MHC class I tetramers and discovered that anti-viral CD8 T cells were not necessarily deleted during chronic viral infections but could instead persist in a functionally inept, exhausted state. This discovery of T cell exhaustion had profound implications for understanding why cell-mediated immunity is ineffective during certain infections and tumors, and for devising checkpoint blockade and other strategies to rejuvenate T cell responses under these conditions. As I established my independent research group at UAB, I went on to show that T cell exhaustion develops in a step-wise and progressive manner and that exhausted T cells are molecularly distinct from their conventional effector and memory counterparts. We also determined how anti-viral CD4 T cells help CD8 T cell responses via the manufacture of IL-21. Our interest in anti-viral CD8 T cell responses goes beyond T cell exhaustion. In published and ongoing studies we are defining the parameters that dictate the development of highly successful, protective CD8 T cell populations, including tumor reactive cells. Our current interests include determining how the functional diversity of the CD8 T cell pool is controlled and contributes to infection and tumor clearance, which is important for the development of immunotherapeutic approaches. In addition to my research activities, I enjoy didactic teaching as well as mentoring undergraduate, graduate, and postdoctoral trainees in the laboratory. I also participate in a variety of committee and service activities that help support my colleagues and foster institutional development.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protectionScience Immunology.  7. 2022
    2022 Editorial overview: Viral immunology before COVID-19Current Opinion in Virology.  52:217-219. 2022
    2020 IL-10–producing Tfh cells accumulate with age and link inflammation with age-related immune suppressionScience Advances.  6. 2020
    2019 IL-21 Controls ILC3 Cytokine Production and Promotes a Protective Phenotype in a Mouse Model of ColitisImmunoHorizons.  3:194-202. 2019
    2019 Immune exhaustion: Past lessons and new insights from lymphocytic choriomeningitis virusViruses.  11. 2019
    2019 Inscribing the core memories of killersCellular and Molecular Immunology.  16:104-105. 2019
    2017 Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infectionNature Immunology.  18:1249-1260. 2017
    2017 Late arising T follicular helper cells cultivate the B cell crop during chronic infectionsScience Immunology.  2. 2017
    2016 IL-10 regulates memory T Cell development and the balance between Th1 and follicular Th cell responses during an Acute Viral InfectionJournal of Immunology.  197:1308-1321. 2016
    2016 IL-21 and T Cell Differentiation: Consider the ContextTrends in Immunology.  37:557-568. 2016
    2016 A context-dependent role for IL-21 in modulating the differentiation, distribution, and abundance of effector and memory CD8 T cell subsetsJournal of Immunology.  196:2153-2166. 2016
    2016 Editorial overview: Viral immunologyCurrent Opinion in Virology.  16:vii-ix. 2016
    2015 A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral ControlCell Reports.  13:1118-1124. 2015
    2015 T cell exhaustion during persistent viral infectionsVirology.  479-480:180-193. 2015
    2014 A stay of execution: Type I Interferons Pardon T cells from death by natural killersImmunity.  40:861-862. 2014
    2014 Effects of atorvastatin and pravastatin on immune activation and T-cell function in antiretroviral therapy-suppressed HIV-1-infected patientsAIDS.  28:2627-2631. 2014
    2014 Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 miceArthritis and Rheumatology.  66:2601-2612. 2014
    2014 Tissue-resident T cells lose their S1P 1 exit visasCellular and Molecular Immunology.  11:221-223. 2014
    2014 Virus-specific CD4 and CD8 T cell responses in the absence of Th1-associated transcription factorsJournal of Leukocyte Biology.  95:705-713. 2014
    2013 Temporal requirements for B cells in the establishment of CD4 T cell memoryJournal of Immunology.  191:6052-6059. 2013
    2013 IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitisJournal of Neuroimmunology.  263:43-54. 2013
    2013 IL-17RA is essential for optimal localization of follicular Th cells in the germinal center light zone to promote autoantibody-producing B cellsJournal of Immunology.  191:1614-1624. 2013
    2013 ICAM-1-dependent tuning of memory CD8 T-cell responses following acute infection 2013
    2013 Anti-viral CD8 T cells and the cytokines that they loveVirology.  435:157-169. 2013
    2011 IL-21 is an antitolerogenic cytokine of the late-phase alloimmune responseDiabetes.  60:3223-3234. 2011
    2011 Exhausted cd8 t cells downregulate the il-18 receptor and become unresponsive to inflammatory cytokines and bacterial co-infectionsPLoS Pathogens.  7. 2011
    2011 Cytokines and the inception of CD8 T cell responsesTrends in Immunology.  32:180-186. 2011
    2011 Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllersJournal of Virology.  85:2316-2324. 2011
    2010 Interleukin-21: A multifunctional regulator of immunity to infections 2010
    2010 IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infectionJournal of Immunology.  185:4835-4845. 2010
    2010 Pronounced virus-dependent activation drives exhaustion but sustains IFN-γ transcript levelsJournal of Immunology.  185:3643-3651. 2010
    2010 Shaping successful and unsuccessful CD8 T cell responses following infectionBioMed Research International.  2010. 2010
    2010 T-cell exhaustion: Characteristics, causes and conversionImmunology.  129:474-481. 2010
    2009 A vital role for Interleukin-21 in the control of a chronic viral infectionScience.  324:1572-1576. 2009
    2008 Memory CD4 T cells emerge from effector T-cell progenitorsNature.  452:356-360. 2008
    2007 HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in miceVaccine.  25:6764-6773. 2007
    2007 Functionally competent antigen-specific Cd127hi memory CD8 + T cells are preserved only in HIV-infected individuals receiving early treatmentJournal of Infectious Diseases.  195:108-117. 2007
    2006 CD127 and virus infectionModern Aspects of Immunobiology.  19:2. 2006
    2006 Bim mediates apoptosis of CD127lo effector T cells and limits T cell memoryEuropean Journal of Immunology.  36:1694-1706. 2006
    2006 In vivo analysis of adenovirus-specific cytotoxic T lymphocyte response in mice deficient in CD28, Fas ligand, and perforinHuman gene therapy. Clinical development.  17:669-682. 2006
    2005 Rapid recruitment of virus-specific CD8 T cells restructures immunodominance during protective secondary responsesJournal of Virology.  79:12703-12713. 2005
    2005 Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation 2005
    2005 Cutting edge: Emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell helpJournal of Immunology.  174:5926-5930. 2005
    2004 Maintenance, Loss, and Resurgence of T Cell Responses during Acute, Protracted, and Chronic Viral InfectionsJournal of Immunology.  172:4204-4214. 2004
    2004 CD4 T Cell-Dependent CD8 T Cell MaturationJournal of Immunology.  172:2834-2844. 2004
    2003 Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: In vitro expression and immune responses in DNA-vaccinated miceAIDS Research and Human Retroviruses.  19:817-823. 2003
    2003 Ablation of CD8 and CD4 T cell responses by high viral loadsJournal of Immunology.  170:477-486. 2003
    2003 Control of lymphocytic choriomeningitis virus infection in granzyme B deficient miceVirology.  305:1-9. 2003
    2002 T cell responses to viral infections: Lessons from lymphocytic choriomeningitis virusImmunologic Research.  26:309-321. 2002
    2002 Elevated generation of reactive oxygen/nitrogen species in hantavirus cardiopulmonary syndromeJournal of Virology.  76:8347-8359. 2002
    2002 Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8+ T cellsJournal of Immunology.  169:1444-1452. 2002
    2001 In vivo selection of a lymphocytic choriomeningitis virus variant that affects recognition of the GP33-43 epitope by H-2Db but not H-2KbJournal of Virology.  75:5099-5107. 2001
    2000 Cutting edge: Increased expression of Bcl-2 in antigen-specific memory CD8+ T cellsJournal of Immunology.  164:3950-3954. 2000
    1999 Impaired anti-viral T cell responses due to expression of the LY49A inhibitory receptorJournal of Immunology.  163:5526-5534. 1999
    1998 Viral immune evasion due to persistence of activated T cells without effector functionJournal of Experimental Medicine.  188:2205-2213. 1998
    1998 Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infectionJournal of Experimental Medicine.  188:71-82. 1998
    1998 Counting antigen-specific CD8 T cells: A reevaluation of bystander activation during viral infectionImmunity.  8:177-187. 1998
    1998 Therapeutic vaccination against chronic viral infection: The importance of cooperation between CD4+ and CD8+ T cellsCurrent Opinion in Immunology.  10:444-449. 1998
    1997 Virus-specific, CD8+ major histocompatibility complex class I- restricted cytotoxic T lymphocytes in lymphocytic choriomeningitis virus- infected β2-microglobulin-deficient miceJournal of Virology.  71:8392-8396. 1997
    1996 Fas-dependent CD4+ cytotoxic T-cell-mediated pathogenesis during virus infection 1996
    1995 Natural killer cell activity in lymphocytic choriomeningitis virus-infected β2-microglobulin-deficient miceInternational Immunology.  7:1545-1556. 1995
    1995 Attenuated mutants of Venezuelan equine encephalitis virus containing lethal mutations in the PE2 cleavage signal combined with a second-site suppressor mutation in E1Virology.  212:102-110. 1995
    1995 The Cell‐Mediated Immune Response Against Lymphocytic Choriomeningitis Virus in β2‐microglobulin Deficient MiceImmunological Reviews.  148:151-168. 1995
    1994 In vitro characterization of an internal ribosomal entry site (IRES) present within the 5' nontranslated region of hepatitis A virus RNA: Comparison with the IRES of encephalomyocarditis virusJournal of Virology.  68:1066-1074. 1994
    1993 Transfer of lymphocytic choriomeningitis disease in β2-microglobulin-deficient mice by CD4+ T cellsInternational Immunology.  5:1193-1198. 1993
    1992 Assignment of mutant tsN19 (complementation group E) of respiratory syncytial virus to the P protein geneJournal of General Virology.  73:865-873. 1992
    1991 Parameters influencing the attachment of hepatitis A virus to a variety of continuous cell linesJournal of General Virology.  72:1667-1675. 1991


    Year Title Altmetric
    2014 Immune Response to Viruses: Cell-Mediated Immunity 2014
    2008 Immune Response to Viruses: Cell-Mediated Immunity.  70-77. 2008
    2006 CD8 T-cell Immunodominance, Repertoire, and Memory.  109-145. 2006

    Research Overview

  • My research program is primarily centered upon understanding why robust and highly effective immune responses are induced by certain infections and vaccinations, and why and how they become defective during persistent infections and cancers. Our studies have shown that virus-specific CD8 T cells succumb to exhaustion during persistent infections, and we have highlighted a vital role for CD4 T cells in supporting CD8 T cell responses. We also discovered that the CD4 T cell-derived cytokine IL-21 is essential for sustaining cell-mediated immunity in chronically infected hosts and that without this cytokine the composition of the virus-specific CD8 T cell pool is corrupted. Additionally, we demonstrated that adhesion molecule interactions influence the balance of effector and memory phenotype cells and also regulate the deletion of virus-specific CD8 T cells during chronic infections. As our projects have advanced a common immunological theme that has emerged is the central role of cytokines, as both intrinsic regulators and predictors of the outcome of the T cell response, and also as extrinsic factors that provoke and direct their development, maintenance, and quality. Consequently, our scientific interests have evolved towards analytically deconvoluting the functional complexity of T cell responses, with a major goal of understanding how the formation of discrete cytokine producing subsets is controlled and how they contribute to the success or failure of anti-pathogen or anti-tumor immunity. We are especially interested in why functional disparities arise as T cell responses develop during the course of an immune response, and determining how this diversification influences signaling and transcriptional networks which shape their differentiation state and the protective efficacy of the T cell pool.
  • Investigator On

  • Adaptive Immunity and Persistent SARS-CoV-2 Replication  awarded by National Cancer Institute/NIH/DHHS
  • Mechanism of Alphavirus Packaging: Designing of Pseudoinfectious Viruses  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Mechanistic Role of ns2 Protein in Evasion of Innate Immune Response by Alphaviruses  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Modeling FCRL6 Regulation and Function in Transgenic Mice  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • New Generation of Efficient Vaccines Against Encephalitogenic Alphaviruses  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Sialylation Dependent Control of CD8 T cell Stemness during Chronic Viral Infection  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • UAB Center for AIDS Research  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • UAB Center for AIDS Research  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • UAB Center for AIDS Research - Administrative Core  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • UAB Center for AIDS Research - Administrative Supplement  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Viral Adaptation to CD4 T Cell Responses and the Impact on HIV Immunity  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Virus-Induced Cell Fate Decisions in Anti-Viral Immunity  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Education And Training

  • Doctor of Philosophy in Microbiological Sciences and Immunology, University of North Carolina System : Chapel Hill 1996
  • Bachelor of Science or Mathematics in Microbiological Sciences and Immunology, University of Warwick 1991
  • Full Name

  • Allan Zajac