CTLA4 (CD152) modulates the Th subset response and alters the course of experimental Leishmania major infection

Eur J Immunol. 1998 Dec;28(12):4213-20. doi: 10.1002/(SICI)1521-4141(199812)28:12<4213::AID-IMMU4213>3.0.CO;2-C.

Abstract

Since both the nature and the amplitude of an antigen-specific T cell response are dependent on co-stimulatory signals, we have investigated the role of CD28/CD152-mediated T cell co-stimulation in the regulation of experimental cutaneous leishmaniasis. CD28-deficient mice and their wild-type littermates are equally susceptible to Leishmania major infection. Whole anti-CD152 antibody significantly exacerbates the disease while anti-CD152 Fab ameliorates the disease in genetically susceptible BALB/c mice but not in C57BL/6, a resistant strain. The anti-CD152-induced exacerbation of the disease is accompanied by increased IL-4-secreting cell number, diminished parasite-specific delayed-type hypersensitivity (DTH) response and augmented anti-2,4,6-trinitrophenyl (TNP) IgG1 in response to TNP-leishmanial antigen crude soluble antigen (CSA), suggesting an exaggerated Th2 type of response. Anti-CD152 Fab-mediated amelioration of the disease is associated with increased IFN-gamma-secreting cell number, increased parasite-specific DTH response and enhanced IgG2a isotype in response to TNP-CSA suggesting a Th1 type of response. Unlike TNP-CSA, TNP-keyhole limpet hemocyanin does not induce the change in Ig isotype, indicating that the immunomodulatory effect of anti-CD152 is antigen specific. Anti-CD152 antibody-induced early change in Th subsets suggests an important role for CD152 in determining the course of L. major infection, perhaps by alteration of Th subset differentiation.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • CTLA-4 Antigen
  • Female
  • Immunoconjugates*
  • Interferon-gamma / immunology
  • Interleukin-4 / immunology
  • Leishmania major*
  • Leishmaniasis, Cutaneous / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Interleukin-4
  • Abatacept
  • Interferon-gamma