Protection from Cryptosporidium parvum infection by gammadelta T cells in mice that lack alphabeta T cells.
OBJECTIVE
Cryptosporidium parvum establishes a parasitic relationship with epithelial cells of the intestine. Infection with this protozoan is resolved in the immunocompetent host, but persistent life-threatening infection develops in the immunocompromised host. We propose that gammdelta T cells in the intestinal mucosa play a role in immunity to C. parvum.


METHODS
Intestinal intra-epithelial lymphocyte and lamina propria T-cell subsets were examined in mice infected with C. parvum. The mice are homozygous for a deletion of the TCRalpha chain gene, TCRalpha(-/-) and, therefore, lack conventional alphabeta T cells, but retain a population of T cells with gammadelta T-cell receptors. To examine the contribution of gammadelta T cells to immunity, these mice were treated with monoclonal antibody GL3-3A, specific for this T-cell receptor, then were inoculated with C. parvum oocysts. Lymphocyte subsets and hematoxylin and eosin (H&E)-stained intestinal sections from untreated mice were compared with those from mice treated with either a low dose of GL3-3A for 6 weeks, or a high dose of GL3-3A for 16 weeks.


RESULTS
The proportion of gammadelta T cells in the lamina propria increased in infected mice. In mice treated with a low dose of GL3-3A, a population of gammadelta T cells that had characteristics of activated cells, was still evident 6 weeks after inoculation. No C. parvum developmental forms were identified in the intestinal sections of mice under these conditions. However, TCRalpha(-/-) mice treated with a high dose of GL3-3A were depleted of gammadelta T cells, and 50% of the mice were infected with C. parvum.


CONCLUSIONS
The gammadelta T cells contribute to protection against C. parvum infection. In the absence of conventional T cells, activation of intestinal gammadelta T cells may prevent infection with this organism.
Eichelberger
M C
MC
Department of International Health, The Johns Hopkins University, Baltimore, MD, USA.
Suresh
P
P
Rehg
J E
JE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003457:Cryptosporidiosis / Q000276:immunology* / Q000517:prevention & control*; D016785:Cryptosporidium parvum / Q000276:immunology* / Q000302:isolation & purification; D004198:Disease Susceptibility; D017353:Gene Deletion; D007082:Ileum / Q000382:microbiology; D051379:Mice; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta