title: SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination.
abstract: HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.
authors.affiliation: Program in Barrier Immunity and Repair, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Carol L
authors.initials: CL
authors.lastname: Vinton
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Lynch
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Canary
authors.forename: Jason
authors.initials: J
authors.lastname: Ho
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Darrah
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: Susan L
authors.initials: SL
authors.lastname: Moir
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D007117:Immunization, Secondary; D018320:Leishmania major / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008253:Macaca mulatta / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D014611:Vaccination / Q000379:methods
chemical_list: D054332:Leishmaniasis Vaccines