INVESTIGADORES
BEKINSCHTEIN Pedro Alejandro
artículos
Título:
Superantigens and murine mammary tumor retrovirus
Autor/es:
ISABEL PIAZZON; IRENE NEPOMNASCHY; VALERIA BUGGIANO; PEDRO BEKINSCHTEIN; ALEJANDRA GOLDMAN; PAULA BERGUER; ADRIANA DEROCHE; GABRIELA LOMBARDI
Revista:
MEDICINA (BUENOS AIRES)
Referencias:
Año: 1997 vol. 57 p. 21 - 33
ISSN:
0025-7680
Resumen:
Hosts and their pathogens have co-evolved for millions of years,
developing multiple and intimate interactions. Vertebrates have evolved
a very complex immune system which pathogens have often been able to
circumvent, in some cases even managing to appropriate some of its
components for their own purpose. Among the pathogens which do use
components of the immune system to survive and propagate, those coding
for the expression of superantigens (SAgs) are now under intense
scrutiny. Investigations concerning one of these pathogens, the mouse
mammary tumor virus (MMTV), led to the understanding of how the
expression of such components is a critical step in their life cycle. A
number of milk-borne exogenous MMTV infect mice shortly after birth
and, when expressed, produce superantigens. Herein, we describe the
biological effects of new variants of MMTV. Two of these, BALB14 and
BALB2 encoding SAgs with V beta 14+ and V beta 2+ specificities,
respectively, were present in BALB/c mice of our colony (BALB/cT); a
third variant, termed MMTV LA, originated in (BALB/cTxAKR)F1 mice from
recombination between BALB 14 and Mtv-7 endogenous provirus. The
recombinant LA virus induces the deletion of V beta 6+ and V beta 8.1+
T cells as a consequence of the acquisition of SAg hypervariable coding
region of Mtv-7. The SAg encoded by MMTV LA strongly stimulates cognate
T cells in vivo leading to a very effective amplification of lymphoid
cells in BALB/c mice, correlating with a high incidence of mammary
tumors. These results suggest that the presence of non-productive
endogenous proviruses--generally considered to confer a selective
advantage to the host by protecting it from infection with exogenous
MMTVs encoding cross-reactive SAgs--could also be advantageous for the
pathogen by increasing its variability, thus broadening the host range
and allowing the expansion of highly tumorigenic variants.